【摘要】

实验目的：据报道，中链脂肪酸（MCFAs）与长链脂肪酸(LCFAs)相比，其致肥胖较少。然而，人们对中链脂肪酸对胰岛素作用的影响研究偏少。在此，我们研究了MCFAs对脂质代谢和胰岛素作用的组织特异性作用。
实验设计和方法: 在4-5周时间内，C57BL6/J小鼠和Wistar大鼠被喂食一种低脂肪食物或含有MCFAs，LCFAs高脂食物，并且测量线粒体氧化能力，脂质水平和胰岛素作用的标记物。

实验结果：饲喂MCFA的小鼠比LCFA喂食的动物表现出更少的肥胖症和良好的葡萄糖耐受性。喂食LCFA的日粮显著增加骨骼肌中甘油三酯水平（77％，P<0.01），但在MCFA喂养的动物中保持与低脂日粮对照组的水平。与低脂日粮喂养的相比，LCFA日粮能够显著增加肌肉中线粒体代谢标记物 (20–50%, P<0.05)；然而在使用MCFA饲喂的动物中，其氧化能力得到了大幅度的增加（与低脂日粮相比增加了50%–140%，P<0.01）。与LCFA日粮组相比，MCFA日粮组肝脏中甘油三酯的积累量更大，原因可能是几种生脂酶的升高。在大鼠中，饲喂等热量含有MCFA或LCFA的高脂日粮可以诱导肝脏胰岛素抵抗到一个相似的水平。然而，胰岛素作用维持在饲喂低脂日粮组肌肉中和饲喂含有MCFA脂肪中的水平。
结果分析：尽管MCFAs在肝中会诱导脂肪变性和胰岛素抵抗，但它可减少肥胖并在肌肉和脂肪中能够维持胰岛素作用。因此含有MCFAs的日粮，可能有利于预防肥胖和外周胰岛素抵抗。
 
以下是实验中的相关图表
 
表1：低脂和高脂日粮的脂肪酸组成
 
表2：小鼠的体重，脂肪比例和组织甘油三酯的水平
 
图1：小鼠饲喂LF，MCFA，和LCFA的前一夜禁食，做葡萄糖耐受测试。A：小鼠腹腔注射葡萄糖后的血液葡萄糖水平（2g/kg）。B：曲线下的增量区域作为葡萄糖清除指标。数据代表真实值±每5-11个小鼠的平均偏差。P<0.01 vs低脂肪；P<0.01vs低脂肪和MCFAs。
 
图2：骨骼肌中氧化酶的活力和收集饲喂含有LF，MCFA，和LCFA食物的小鼠的肝脏，数据表示真实值±每5-6只小鼠的平均偏差。P<0.01 vs低脂肪和LCFAs；P<0.01 vs.低脂肪。
 
图3：免疫印迹用于骨骼肌中线粒体代谢和生物起源的标志物，同时收集饲喂含有LF，MCFA，和LCFA食物的小鼠的肝脏。通过SDS-PAGE分析等量的肌肉裂解物（10-20μg蛋白质），并用针对PGC-1α，CPT-1，UCP3的特异性抗体和线粒体呼吸链亚基进行免疫印迹。对6个表达动物进行密度分析（与低脂对照相关）。P<0.05；P<0.01 vs.低脂肪；P<0.05；P<0.01vs.MCFAs。
 
 
图4：采集饲喂低脂（LF）、MCFA和LCFA食物小鼠的肝脏，并且对肝中生脂酶进行免疫印迹，通过SDS-PAGE分析等量的肝脏裂解物（10-20μg蛋白质），并用针对FAS, ACC, 和SCD-1的特异性抗体进行免疫印迹。

 
表3：大鼠体重，脂肪比例，循环系统参数，和组织甘油三酯的水平
 
表4：代谢参数来源于小鼠的高胰岛素-正常血糖钳夹实验
 
         总的来说，本研究表明含有MCFAs高脂日粮对组织特异的胰岛素敏感性具有不一致的作用，在肌肉和脂肪组织中保持胰岛素作用与低脂日粮饲喂对照组在同一个水平的前提下，低脂日粮的对照组诱导胰岛素抗性的程度与肝脏中的LCFAs相似。MCFA对肌肉中胰岛素作用的保留与线粒体生物合成的有效刺激相关，它可以有效地防止脂质在组织中的积累。鉴于当前研究使用的膳食脂肪总量相对较高（占总摄入能量的45-60％），在下一步的研究中需要确定对能量代谢和胰岛素作用产生有益影响所需膳食MCFAs的量（同时以绝对值和相对于日粮LCFAs值）和该日粮MCFAs的量是否能避免肝脏中脂肪积聚。在这方面，一些关于人体的研究已经报道了低剂量MCFA对机体的能量消耗和身体组成起到积极效应的案例。此外，一些糖尿病治疗药物（例如二甲双胍）可以通过它们在肝脏中的发挥其胰岛素增敏作用，因此，研究MCFA的添加是否对多种胰岛素靶向组织中的胰岛素作用效果增强相关具有很大的意义。 OBJECTIVE—Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action.
RESEARCH DESIGN AND METHODS—C57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4–5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured.
RESULTS—Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%,P<0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20–50%, P<0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet–fed controls; however; the increase in oxidative capacity was substantially greater in MCFA-fed animals (50–140% versus low-fat–fed controls, P<0.01). The MCFA diet induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic enzymes. In rats, isocaloric feeding of MCFA or LCFA high-fat diets induced hepatic insulin resistance to a similar degree;however, insulin action was preserved at the level of low-fat diet–fed controls in muscle and adipose from MCFA-fed animals.
CONCLUSIONS—MCFAs reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance in the liver. Dietary supplementation with MCFAs may therefore be beneficial for preventing obesity and peripheral insulin resistance.
  In summary, our study shows that high-fat diets containing MCFAs have divergent effects on tissue-specific insulin sensitivity, inducing insulin resistance to a similar degree as LCFAs in liver while preserving insulin action at the level of low-fat-fed controls in muscle and adipose tissue The preservation of muscle insulin action by MCFAs is associated with a potent stimulation of mitochondrial biogenesis, which appears to be sufficient to prevent lipid accumulation in this tissue. Given that the total amount of dietary fat used in the current studies is relatively high (i.e., 45–60% of energy), it will be important to determine in future studies the amount of dietary MCFAs (both in absolute terms and relative to dietary LCFAs) required for beneficial effects on energy metabolism and insulin action and whether this amount of dietary MCFAs avoids liver lipid accumulation. In this regard, some human studies (21,46,47) have reported positive effects on energy expen diture and body composition with relatively low dietary doses of MCFAs. Additionally, as some antidiabetes ther apies (e.g., metformin) are known to exert the majority of
their insulin-sensitizing effects via their actions in the liver (48), it will be of interest to determine whether MCFA supplementation in conjunction with such agents results in beneficial effects on insulin action in multiple insulin target tissues.











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